The term "alcoholic hepatitis" denotes a disease characterized histologically by fatty metamorphosis of hepatocytes, polymorphonuclear leukocytic infiltrates, fibrosis and cellular necrosis and clinically by moderate-to-severe impairment of liver function and substantial mortality (30-40%). It is clearly a manifestation of ethanol toxicity and is common. Nonetheless, its pathogenesis is obscure. Despite a voluminous literature on the metabolic effects of ethanol in the liver, there are few clues as to the initiation of the inflammatory lesion of alcoholic hepatitis. Preliminary studies by investigators at the Liver Center Laboratory at San Francisco General Hospital have revealed that normal hepatocytes (rat and human) in primary culture and rats in vivo elaborate a potent chemoattractant for polymorphonuclear leukocytes when incubated with modest concentrations of ethanol. This factor appears to be a polar lipid, perhaps an arachidonic acid metabolite generated by a free radical-mediated mechanism. Because this response occurs at relatively low levels of ethanol (5-10 mM) and is rapid it suggests that leukocytic infiltrates play a primary role in the injury response of the liver. By elaborating oxygen- derived free radicals and extracellular matrix degrading enzymes leukocytes may be responsible for much of the damage in the affected liver. The work outlined to test this hypothesis involves parallel studies of the nature and production of the chemotactic factor and the role of leukocytes in mediating changes in hepatocyte and endothelial cell function including so called "capillarization of the sinusoids." The findings are expected to provide new insights into the precise sequence of pathologic events in alcoholic hepatitis and to help rationalize therapy for this serious disease.